We seek in this project to advance understanding of the role of corticotropin releasing hormone (CRH) in normal physiology and in disorders of pituitary-adrenal function. Rapid progress in this area has been made possible by the recent discovery of the chemical structure of CRH. Our objectives are to determine the dose-response relationship for CRH in primates and in humans, to study the metabolic clearance rate of CRH in primates and in man, to develop methods to measure CRH accurately in tissue and in biological fluids, to measure CRH in the plasma and cerebrospinal fluid of patients with Cushing's disease, to develop a clinical CRH test and to evaluate its usefulness in adrenal insufficiency and Cushing's disease, and to develop methods to measure CRH receptors so that we can explore the role of receptor regulation as a modulator of tissue sensitivity to CRH.